Objective To establish a high-performance liquid chromatography tandem mass spectrometry(HPLC-MS/MS)method for determining the plasma concentration of olverembatinib in leukemia patients,apply it to clinical drug monitoring,and provide reliable basis for rational drug use in clinical practice.Methods Ponatinib-d8 was used as an internal standard,and methanol was used to precipitate plasma proteins and extract olverembatinib.The chromatographic column was Welch Ultimate XB-C18 cloumn(50 mmx4.6 mm,5 μm),with a column temperature of 60 ℃.The mobile phase consisted of an aqueous solution(containing 0.1％formic acid+2 mmol/L ammonium acetate)-methanol solution(containing 0.1％formic acid),with a flow rate of 0.8 mL/min and gradient elution.Electrospray positive ion mode was used,with multiple reaction monitoring scanning.The quantitative ion pair of olverembatinib was m/z 533.3→260.1,the qualitative ion pair was m/z 533.3→433.3,and the internal standard ion pair was m/z 541.1 →260.2.The plasma samples of 40 leukemia patients taking olverembatinib were monitored and analyzed for concentration,and IBM SPSS Statistics 27.0 and OriginPro 2021 softwares were used for statistical analysis of the results.Results The linear range of olverembatinib was 1-250 ng/mL(r=0.998 0),the lower limit of quantification was 1 ng/mL,the extraction recovery rate was 100.28％～101.27％,the intra-day precision RSD was 1.15％～3.87％,and the inter-day precision RSD was 2.32％～3.68％.Conclusion This method is easy to operate,highly specific and sensitive,and can be used to determine the blood concentration of olverembatinib in leukemia patients.

Objective To establish a high-performance liquid chromatography tandem mass spectrometry(HPLC-MS/MS)method for determining the plasma concentration of methylprednisolone in patients with hematological diseases,and apply it to guide the clinical application.Methods Plasma samples were subjected to methanol-precipitated protein containing internal standard methylprednisolone-d3.The HPLC system was equipped with an Ultimate XB-C18(4.6mm×50mm,5 μm particle size),maintained at 60℃,and 5 μl of the supernatant was injected.Mobile phases consisting of 0.1%(v/v)formic acid(1∶1 000)and 2 mmol/L ammonium acetate in water(B)and 0.1%(v/v)formic acid(1∶1 000)in methanol at a flow rate of 0.8 ml/min was used.The electrospray ionization(ESI)source was operating in positive ion mode.Multiple reaction monitoring(MRM)was applied for the detection of the components:Methylprednisolone mass-to-charge ratio(m/z)375.4 → 339.4(qualitative ions),methylprednisolone m/z 375.4→357.3(quantitative ions),methylprednisolone-d3 m/z 378.2→360.3.The peak area ratio of methylprednisolone to methylprednisolone-d3 was used as the quantitative basis.The concentration of methylprednisolone in plasma was calculated and its performance was investigated.Results The linear range of methylprednisolone was 10～1 000ng/ml(r2=0.996 7),and the lower limit of quantification was 10 ng/ml.The RSDs of intra-day and inter-day precision results were less than 15%and the relative recovery ranged from 99.52%～104.79%.For methylprednisolone,the samples were stable at-20℃after three repeated freeze-thaw cycles.The prepared samples were stable at room temperature and 4℃for 24h(RSDs<15%).The steady-state blood drug concentrations of methylprednisolone in 16 patients were in the ranges of 1～258 ng/ml.Conclusion The HPLC-MS/MS method can accurately,rapidly and simply detect the concentration of methylprednisolone,and be suitable for clinical application.

Objective:To observe the effect of early weightbearing after anterior cruciate ligament reconstruction (ACLR) on lower limb motor function, activation of the knee muscles and the stability of the knee joint.Methods:Forty-four persons who had received ACLR were divided at random into a control group and an experiment group, each of 22. In addition to conventional rehabilitation treatment after surgery, the control group underwent weightbearing training from the 8th day after the surgery, while the experimental group began weight-bearing training from the 3rd postoperative day. Both groups had their motor functioning evaluated using the International Knee Scoring Committee (IKDC) knee subjective evaluation form 3 days after the operation, and then 6 and 12 weeks later. Their pain perceptions were quantified on the same schedule using visual analogue scoring (VAS), and protractor measurements documented active range of motion (AROM). Electromyography (AEMG) of the medial head and rectus femoris muscle was also performed, and the stability of the knee joint was assessed using the KT-1000 test.Results:After the intervention, the average IKDC score, VAS score, knee extension and flexion AROMs, medial quadriceps head AEMG ratio, and rectus femoris muscle AEMG ratio improved to different degrees in the two groups. At 6 weeks the average pain score, knee extension and flexion ranges of motion, quadriceps medial head AEMG ratio, and rectus femoris AEMG ratio of the experimental group were all better than the control group′s averages. At 12 weeks the average IKDC subjective knee function score in the experimental group was also superior.Conclusions:Supplementing conventional rehabilitation with early weight-bearing can significantly improve the recovery from anterior cruciate ligament reconstruction. Beginning on day 3 after the operation gives the best results.

Objective:To learn about the iodine nutrition level of school-age children aged 8 - 10 in Shaanxi Province.Methods:From 2017 to 2020, in counties (cities, districts) under the jurisdiction of Shaanxi Province, one township (street) was selected from five directions: East, West, South, North and Middle, one primary school was selected from each township (street), and 42 non-boarding school-age children aged 8 - 10 (age balanced, half male and half female) were selected from each primary school. Random urine samples of children were collected once, and urinary iodine was detected by arsenic-cerium catalytic spectrophotometry.Results:A total of 91 766 children's urine samples were tested from 2017 to 2020, and the median urinary iodine was 221.7 μg/L. Urinary iodine < 100 μg/L accounted for 10.4% (9 554/91 766), 100 - < 200 μg/L accounted for 32.3% (29 602/91 766), 200 - < 300 μg/L accounted for 30.6% (28 065/91 766), and ≥300 μg/L accounted for 26.7% (24 545/91 766). The median of children's urinary iodine in each year was 228.5, 218.0, 211.7, and 230.1 μg/L, respectively, the difference between years was statistically significant ( H = 278.66, P < 0.001). Conclusion:From 2017 to 2020, the iodine nutrition of school-age children aged 8 - 10 in Shaanxi Province is generally in an ultra-suitable state.

Objective:To evaluate the accuracy of glomerular filtration rate (GFR) assessed from the renal dynamic imaging method (Gates method) with 99Tc m-diethylene triamine pentoacetic acid (DTPA) in the heart transplant population. Methods:From September 2017 to June 2018, 34 patients with advanced heart failure who were prepared for surgery (30 males, 4 females; age: (45±14) years; heart transplant group) and 41 patients with normal heart function (19 males, 22 females; age: (50±17) years; control group) in Fuwai Hospital were respectively enrolled. GFRs of all patients were measured using Gates method (gGFR) and dual plasma sample method (DPSM; dGFR) with 99Tc m-DTPA. The accuracy of Gates method for detecting GRF was verified by using DPSM as the reference. Seventeen patients in heart transplant group underwent 99Tc m-DTPA renal dynamic imaging for Gates and DPSM results repeatedly after the surgery. The single kidney (left and right) functions (dGFRL and dGFRR) of DPSM were obtained according to the results of Gates method. Pearson correlation analysis and paired t test were used to analyze the data. Results:The gGFR in heart transplant group was higher than dGFR ((66.49±15.66) vs (49.16±13.24) ml·min -1·1.73 m -2; t=6.728, P<0.01), and there was a moderate correlation between them ( r=0.467, P<0.01). No difference between gGFR and dGFR in control group was observed ((65.35±26.28) vs (62.22±21.37) ml·min -1·1.73 m -2; t=1.268, P=0.212), and there was a good correlation between them ( r=0.799, P<0.01). The difference between 2 correlation coefficients was statistically significant ( z=-2.44, P<0.05). Serum creatinine decreased, while dGFR, dGFRL and dGFRR increased after the surgery, suggesting the improved renal function. Conclusions:The renal dynamic imaging method (Gates method) with 99Tc m-DTPA has less accuracy in the heart transplant patients. Combination of DPSM and Gates method can provide the precise total GFR and assess single kidney GFR, and may serve as a tool to monitor the renal function for the heart transplant patients in clinic.

Endotoxemia is a pathophysiological manifestation caused by the release of large amounts of endotoxin from bacteria in the blood or in the lesion. It can cause multiple organ failure, irreversible shock, and even death. The mortality rate of endotoxemiaIt is high. Bacterial endotoxin is the main cause of endotoxemia. At present, there is no safe and effective drug to treat endotoxemia in clinic. Research shows that blood purification can effectively reduce endotoxin level in the blood, then achieve the goal of treatment of endotoxemia. In this paper, the pathogenesis of endotoxemia, the development of hemoperfusion therapy technology, the mechanism and research status of endotoxin adsorption by different hemoperfusion resin were discussed, and the performance and safety requirements of hemoperfusion adsorbent materials for endotoxemia treatment were studied, so as to provide theoretical support for the synthesis of new hemoperfusion adsorption materials for the treatment of endotoxemia.

OBJECTIVETo observe the effect of crocetin on autophagy in rat hepatocytes exposed to lipopolysaccharide (LPS) and D-galactosamine (D-gal) and explore the mechanism.

METHODSCultured rat hepatocytes were exposed to LPS (1 mg/L) and Dgal (60 mg/L) to induce cell injury and treated with crocetin, 3MA, or crocetin+3MA. Twelve hours after the treatments, the cells were examined for levels of ALT, AST and LDH in the supernatant using ELISA. LC3 fluorescence in the cells following immunofluorescence staining was observed using fluorescence microscopy. Autophagosomes in the cells were observed by transmission electron microscopy, and the cellular expressions of LC3, p62 and SIRT1 were detected using Western blotting.

RESULTSThe levels of ALT, AST and LDH in the hepatocytes were elevated after LPS- and D-gal-induced injury, reached the highest levels after 3MA treatment, but were decreased significantly by crocetin treatment. LC3 fluorescence increased obviously in the injured hepatoctyes, and the increment was the most obvious in crocetin-treated cells; LC3 fluorescence was decreased significantly after 3MA treatment. Cell injury induced obvious increase in autophagy in the hepatocytes, and the number of autophagosomes increased significantly after crocetin treatment but was reduced significantly after 3MA treatment. The cell injury caused an obvious up-regulation of LC3 and SIRT1 expression and down-regulated p62 expression. LC3 and SIRT1 expression levels were the highest and the expression of p62 was the lowest in cells with crocetin treatment. 3MA treatment significantly reduced the expression of LC3 and SIRT1 and increased the expression of p62 in the injured cells.

CONCLUSIONSAutophagy is increased in injured rat hepatocytes, and crocetin can promote autophagy in the injured cells to reduce further cell injury.

Objective To explore the association between the structural patterns of orbitofrontal sulcogyral pattern (OSP)and the susceptibility to schizophrenia in children and adolescents patients with schizophrenia. Methods Seventy-two childhood and adolescence schizophrenia aged 6~18 years were enrolled as the case group and 78 sex-, age-, education-matched healthy children served as the control group. MR images were acquired with a 3.0 T Magnetom Symphony MRI system. Positive and Negative Syndrome Scale (PANSS) was used to evaluate the symptom severity of patients.The pattern type of OFC was classified based on continuity among medial (MOS),lateral (LOS)and transverse (TOS) orbital sulci according to the method of Chiavaras and Petrides'. The orbitofrontal cortex (OFC) sulcogyral pattern was classified into three types(TypeⅠ,TypeⅡ,TypeⅢ)in each hemisphere. Results There were significant differences in the distribution of OFC patterns between the control and the case group (Left hemisphere: Χ2=6.668,P=0.036; Right hemisphere: Χ2=7.501,P=0.024). The linear regression analysis showed that Type Ⅲ in either hemisphere was associated with more severe symptoms in schizophrenia patients (B=7.214, P=0.008). Conclusions Type Ⅲ sulcogyral pattern may be a morphological risk marker for schizophrenia. Compared to the other two types, the Type Ⅲ expression is associated with more severe clinical symptoms.

Objective To study the effect of combined atorvastatin and ezetimibe pretreatment on perioperative hs-CRP after elective PCI.Methods One hundred and fifty-six patients with typical chronic stable angina pectoris were randomly divided into atorvastatin treatment group (n=78) and combined atorvastatin and ezetimibe treatment group (n=78).Their serum hs-CRP,TC and LDL-C level was measured before PCI,at hours 8,24,48 and on day 7 after PCI.Results In comparision with pre-operation,the serum TC and LDL-C levels were significantly lower in two groups (P＜0.01) and in combined atorvastatin and ezetimibe treatment group than in atorvastatin treatment group on day 7 after PCI (P＜0.05).The serum hs-CRP level was significantly higher in two groups at 8 h after PCI than before PCI,reached its peak at 24 h after PCI,continued to increase at 48 h after PCI (P＜0.01),no significant difference was found between the two groups on day 7 after PCI (P＞0.05).The average serum hs-CRP level was lower in combined atorvastatin and ezetimibe treatment group than in atorvastatin treatment group at hours 8,24 and 48 after PCI (P＜0.05) with no significant change found between the two groups on day 7 after PCI (P＞0.05).Conclusion The effect of combined atorvastatin and ezetimibe pretreatment is better than that of atorvastatin alone on perioperative acute inflammatory reactions after PCI.

Objective To study the liver protection of crocetin against paraquat (PQ) poisoning induced acute liver injury in rats. Methods Fifty-four male Wistar rats were randomly divided into control group, exposure group and treatment group, and the rats in each group were subdivided into the 0.5th, 2nd, and 6th day after exposure subgroups (n = 6). The model of acute liver failure induced by PQ poisoning was reproduced by intraperitoneal injection of 20 mg/kg of 20% PQ, and the rats in control group was injected with the same amount of normal saline. The rats in treatment group were given with intraperitoneal injection of 50 mg/kg crocetin after 0.5 day, once a day until they were sacrificed; the other two groups were injected with the same amount of normal saline. The rats in all groups were sacrificed at the corresponding time points, and blood was collected from inferior vena cava and hepatic tissue was harvested. Hematoxylin and eosin (HE) staining was used to observe the pathological changes in liver tissue on the 6th day under light microscope. Enzyme linked immunosorbent assay (ELISA) was used to detect the serum tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) levels. Reverse transcription-polymerase chain reaction (RT-PCR) was used to detect the mRNA expressions of inducible nitric oxide synthase (iNOS) and nuclear factor-κB (NF-κB). The activities of apoptosis related factors, including caspase-8, -9, -12, in hepatic tissue were determined on the 6th day with chromogenic substrate method. Results In the liver tissue of exposed group, extensive infiltration of the inflammatory cells and the diffuse fragments necrosis were visible, and the regeneration of the liver cells was not obvious, and severity of the injury in a time dependent way. In the treatment group, the structure of hepatic artery was visible, and the infiltration of necrosis, congestion and inflammatory cells were not obvious. On the 0.5th, 2nd, and 6th day, serum levels of IL-6 and TNF-α, the mRNA expressions of iNOS and NF-κB in liver tissue, and the caspase-8, -9, -12 activities on the 6th day in the exposure group and treatment group were significantly higher than those in the control group. And the parameters in treatment group were significantly lower than those of the exposure group [IL-6 (ng/L): 188.37±64.21 vs. 376.61±82.42 on the 0.5th day, 287.18±58.69 vs. 432.77±96.28 on the 2nd day, 234.24±10.17 vs. 375.41±37.59 on the 6th day; TNF-α (ng/L): 472.36±76.43 vs. 688.33±102.19 on the 0.5th day, 189.32±87.54 vs. 296.21±89.77 on the 2nd day, 99.28±16.13 vs. 168.41±66.78 on the 6th day; iNOS mRNA (gray value): 2.998±0.801 vs. 3.453±0.026 on the 0.5th day, 3.126±0.306 vs. 5.259±0.153 on the 2nd day, 0.841±0.135 vs. 1.225±0.057 on the 6th day; NF-κB mRNA (gray value): 1.569±0.818 vs. 2.361±0.063 on the 0.5th day, 2.345±0.489 vs. 4.668±0.368 on the 2nd day, 2.348±0.316 vs. 3.972±0.449 on the 6th day; caspase-8 (pmol/mg): 126.77±9.97 vs. 199.18±66.48 on the 6th day; caspase-9 (pmol/mg): 213.12±69.06 vs. 321.62±89.39 on the 6th day; caspase-12 (pmol/mg): 183.46±70.52 vs. 219.68±53.93 on the 6th day, all P < 0.05]. Conclusion Crocetin has protective effect on liver in rats with PQ poisoning, which role is related with reducing the blood level of inflammatory factors, inhibiting the hepatic caspase-8, -9, -12 activities and gene expressions of iNOS and NF-κB.